This study tested the potential antidepressant activity of minocycline alone or combined with two traditional antidepressant drugs or several glutamate receptor antagonists, using the time sampling method in the forced swimming test. Results showed that: desipramine (10.0 mg/kg, P<0.05; 15.0 mg/kg, P<0.05), minocycline (60.0 mg/kg, P<0.05; 80.0 mg/kg, P<0.05) and EMQMCM (1.5 mg/kg, P<0.05; 2.0 mg/kg, P<0.05), reduced immobility by increasing climbing. Fluoxetine (20.0 mg/kg, P<0.05; 25.0 mg/kg, P<0.05) reduced immobility by increasing swimming. MTEP (5.0 mg/kg, P<0.05; 10.0 mg/kg, P<0.05) and dizolcipine (1.0 mg/kg, P<0.05; 1.5 mg/kg, P<0.05) reduced immobility by increasing swimming and climbing. Combination experiments showed that a subthreshold dose of minocycline (50.0 mg/kg) synergized the antidepressant-like actions of subthreshold doses of: desipramine (5.0 mg/kg; P<0.05), EMQMCM (0.6 mg/kg; P<0.05), MTEP (2.5 mg/kg; P<0.05) and dizolcipine (0.5 mg/kg; P<0.05). In conclusion, minocycline produced antidepressant-like actions in the FST and subthreshold dose of minocycline combined with subthreshold dose of desipramine and several glutamate receptor antagonists and produced antidepressant-like actions.